{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:56:42Z","timestamp":1794013002642,"version":"4.8.0"},"reference-count":123,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Regulatory T cells (Tregs) display metabolic fitness to adopt tumour microenvironment (TME), characterized by hypoxia, acidity and metabolic depletion\/competition, in order to impair anti\u2010tumour immunity and allow metastasis. Tregs and other TME immune cells interact metabolically, with glycolysis supporting proliferation of Tregs along with cancer cells and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and a basal oxidative phosphorylation (OXPHOS) promoting Treg and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activity. Lactate is a glycolysis byproduct that its accumulation creates acidosis within TME, and its uptake provides a fuel source for Treg activity and fosters their persistence in the hypoxic TME. Itaconate and hypoxic TME increase succinate accumulation, but they take complex roles on Tregs and T cells. Hypoxia and hypoxia inducible factor\u20101 (HIF\u20101) activity induce lactate release and Treg recruitment\/accumulation via stimulating glycolysis path and extracellular adenosine aggregation. Knockout of HIF\u20101\u03b1 although reduces lactate, it secondarily induces OXPHOS to fulfil Treg immunosuppressive function. FOXP3 is stabilized by mitochondrial transcription factor A (Tfam) and induces Treg CD36 and OXPHOS, which can be disturbed by nucleus accumbens\u2010associated protein 1 (NAC1). Liver kinase B1 (LKB1) and AMP\u2013activated protein kinase (AMPK) although induce FOXP3 stability and OXPHOS in Tregs, their activities downregulate programmed death\u20101 (PD\u20101) in such cells. OXPHOS augmentation (by \u03b1\u2010ketoglutarate [\u03b1KG]) or suppression (by metformin) disrupt Treg metabolism. Finally, indoleamine 2,3\u2010dioxygenase (IDO) seems to affect Tregs and can be a promising target in advanced immunotherapy na\u00efve cancer patients. The focus of this review is to describe Treg metabolic regulators\/connectome and opportunities they bring about in cancer therapy.\n                  <\/jats:p>","DOI":"10.1111\/imm.70096","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T01:35:22Z","timestamp":1766972122000},"page":"686-700","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Regulatory T Cell Metabolism in Cancer"],"prefix":"10.1111","volume":"177","author":[{"given":"Keywan","family":"Mortezaee","sequence":"first","affiliation":[{"name":"Department of Anatomy School of Medicine, Kurdistan University of Medical Sciences  Sanandaj Iran"},{"name":"Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences  Sanandaj 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